tbuckley/cabot-search huggingface dataset:
Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillance
Authors: Ross Hamblin, Ashley Vardon, Josephine Akpalu, Metaxia Tampourlou, Ioannis Spiliotis, Emilia Sbardella, Julie Lynch, Vani Shankaran, Akash Mavilakandy, Irene Gagliardi, Sara Meade, Claire Hobbs, Alison Cameron, Miles J Levy, John Ayuk, Ashley Grossman, Maria Rosaria Ambrosio, Maria Chiara Zatelli, Narendra Reddy, Karin Bradley, Robert D Murray, Aparna Pal, Niki Karavitaki
Journal: The Lancet Diabetes & Endocrinology (2022)

Radiotherapy is a valuable treatment in the management algorithm of pituitary adenomas and craniopharyngiomas. However, the risk of second brain tumour following radiotherapy is a major concern. We assessed this risk using non-irradiated patients with the same primary pathology and imaging surveillance as controls.In this multicentre, retrospective cohort study, 4292 patients with pituitary adenoma or craniopharyngioma were identified from departmental registries at six adult endocrine centres (Birmingham, Oxford, Leeds, Leicester, and Bristol, UK and Ferrara, Italy). Patients with insufficient clinical data, known genetic predisposition to or history of brain tumour before study entry (n=532), and recipients of proton beam or stereotactic radiotherapy (n=81) were excluded. Data were analysed for 996 patients exposed to 2-dimensional radiotherapy, 3-dimensional conformal radiotherapy, or intensity-modulated radiotherapy, and compared with 2683 controls.Over 45 246 patient-years, second brain tumours were reported in 61 patients (seven malignant [five radiotherapy, two controls], 54 benign [25 radiotherapy, 29 controls]). Radiotherapy exposure and older age at pituitary tumour detection were associated with increased risk of second brain tumour. Rate ratio for irradiated patients was 2·18 (95% CI 1·31-3·62, p<0·0001). Cumulative probability of second brain tumour was 4% for the irradiated and 2·1% for the controls at 20 years.Irradiated adults with pituitary adenoma or craniopharyngioma are at increased risk of second brain tumours, although this risk is considerably lower than previously reported in studies using general population controls with no imaging surveillance. Our data clarify an important clinical question and guide clinicians when counselling patients with pituitary adenoma or craniopharyngioma on the risks and benefits of radiotherapy.Pfizer.
Reply to the correspondence: Bacillus Calmette‐Guérin vaccination to prevent childhood asthma—A revised analysis
Authors: Samidi Navaratna, John Burgess, Nilakshi Waidyatillake, Rachel L. Peters, Shyamali C. Dharmage, Caroline J. Lodge
Journal: Allergy (2022)

The authors have no conflict of interest to declare.
A Phase IIb Randomized Clinical Study of an Anti-α<sub>v</sub>β<sub>6</sub> Monoclonal Antibody in Idiopathic Pulmonary Fibrosis
Authors: Ganesh Raghu, Majd Mouded, Daniel C. Chambers, Fernando J. Martinez, Luca Richeldi, Lisa H. Lancaster, Mark J. Hamblin, Kevin F. Gibson, Ivan O. Rosas, Antje Prasse, Guolin Zhao, Michael Serenko, Natasha Novikov, Amy McCurley, Prashant Bansal, Christopher Stebbins, Million Arefayene, Stella Ibebunjo, Shelia M. Violette, Diana Gallagher, Jürgen Behr
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Treatment options for idiopathic pulmonary fibrosis (IPF) are limited. Objectives: To evaluate the efficacy and safety of BG00011, an anti-αvβ6 IgG1 monoclonal antibody, in the treatment of patients with IPF. Methods: In a phase IIb randomized, double-blind, placebo-controlled trial, patients with IPF (FVC ⩾50% predicted, on or off background therapy) were randomized 1:1 to once-weekly subcutaneous BG00011 56 mg or placebo. The primary endpoint was FVC change from baseline at Week 52. Because of early trial termination (imbalance in adverse events and lack of clinical benefit), endpoints were evaluated at Week 26 as an exploratory analysis. Measurements and Main Results: One hundred six patients were randomized and received at least one dose of BG00011 (n = 54) or placebo (n = 52). At Week 26, there was no significant difference in FVC change from baseline between patients who received BG00011 (n = 20) or placebo (n = 23), least squares mean (SE) −0.097 L (0.0600) versus −0.056 L (0.0593), respectively (P = 0.268). However, after Week 26, patients in the BG00011 group showed a worsening trend. Eight (44.4%) of 18 who received BG00011 and 4 (18.2%) of 22 who received placebo showed worsening of fibrosis on high-resolution computed tomography at the end of treatment. IPF exacerbation/or progression was reported in 13 patients (all in the BG00011 group). Serious adverse events occurred more frequently in BG00011 patients, including four deaths. Conclusions: The results do not support the continued clinical development of BG00011. Further research is warranted to identify new treatment strategies that modify inflammatory and fibrotic pathways in IPF. Clinical trial registered with www.clinicaltrials.gov (NCT03573505).
Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: The CaReMe CKD study
Authors: Johan Sundström, Johan Bodegard, Andreas Bollmann, Marc G. Vervloet, Patrick B. Mark, Avraham Karasik, Tiago Taveira-Gomes, Manuel Botana, Kåre I. Birkeland, Marcus Thuresson, Levy Jäger, Manish M. Sood, Gijs VanPottelbergh, Navdeep Tangri
Journal: The Lancet Regional Health - Europe (2022)

Digital healthcare systems data could provide insights into the global prevalence of chronic kidney disease (CKD). We designed the CaReMe CKD study to estimate the prevalence, key clinical adverse outcomes and costs of CKD across 11 countries. Individual-level data of a cohort of 2·4 million contemporaneous CKD patients was obtained from digital healthcare systems in participating countries using a pre-specified common protocol; summarized using random effects meta-analysis. CKD and its stages were defined in accordance with current Kidney Disease: Improving Global Outcomes (KDIGO) criteria. CKD was defined by laboratory values or by a diagnosis code. The pooled prevalence of possible CKD was 10·0% (95% confidence interval 8.5‒11.4; mean pooled age 75, 53% women, 38% diabetes, 60% using renin-angiotensin-aldosterone system inhibitors). Two out of three CKD patients identified by laboratory criteria did not have a corresponding CKD-specific diagnostic code. Among CKD patients identified by laboratory values, the majority (42%) were in KDIGO stage 3A; and this fraction was fairly consistent across countries. The share with CKD based on urine albumin-creatinine ratio (UACR) alone (KDIGO stages one and two) was 29%, with a substantial heterogeneity between countries. Adverse events were common; 6·5% were hospitalized for CKD or heart failure, and 6·2% died, annually. Costs for renal events and heart failure were consistently higher than costs for atherosclerotic events in CKD patients across all countries. We estimate that CKD is present in one out of ten adults. These individuals experience significant adverse outcomes with associated costs. The prevalence of CKD is underestimated when using diagnostic codes alone. There is considerable public health potential in diagnosing CKD and providing treatments to those currently undiagnosed. The study was sponsored by AstraZeneca.
Barriers and solutions to implementing a multisectoral action plan to prevent and control non-communicable diseases within UNRWA settings: a mixed-methods study
Authors: Shatha Albeik, Suha Saleh, Yassir Turki, Ayoub Mousa, Nada Abu Kishk, Mengxin Tan, Yousef Shahin, Akihiro Seita
Journal: The Lancet (2022)
Multimorbidity patterns and risk of hospitalisation in children: A population cohort study of 3.6 million children in England, with illustrative examples from childhood cancer survivors
Authors: Sheng-Chia Chung, Stefanie Mueller, Katherine Green, Wai Hoong Chang, Darren Hargrave, Alvina G. Lai
Journal: The Lancet Regional Health - Europe (2022)

Population-level estimates of hospitalisation risk in children are currently limited. The study aims to characterise morbidity patterns in all children, focusing on childhood cancer survivors versus children without cancer.Employing hospital records of children aged <19 years between 1997 to 2018 in England, we characterised morbidity patterns in childhood cancer survivors compared with children without cancer. The follow-up began on the 5th anniversary of the index hospitalisation and the primary outcome was the incidence of comorbidities.We identified 3,559,439 eligible participants having 12,740,666 hospital admissions, with a mean age at study entry of 11.2 years. We identified 32,221 patients who survived for at least 5 years since their initial cancer diagnosis. During the follow-up period and within the whole population of 3.6 million children, the leading conditions for admission were (i) metabolic, endocrine, digestive renal and genitourinary conditions (84,749, 2.5%), (ii) neurological (35,833, 1.0%) and (iii) musculoskeletal or skin conditions (23,574, 0.7%), fever, acute respiratory and sepsis (22,604, 0.7%). Stratified analyses revealed that females and children from socioeconomically deprived areas had a higher cumulative incidence for morbidities requiring hospitalisation (p < 0.001). At baseline (5 years after the initial cancer diagnosis or initial hospitalisation for survivors and population comparisons, respectively), cancer survivors experienced a higher prevalence of individual conditions and multimorbidity (≥ 2 morbidities) compared with children without cancer. Cox regression analyses showed that survivors had at least a 4-fold increase in the risk of hospitalisation for conditions such as chronic eye conditions (hazard ration (HR):4.0, 95% confidence interval (CI): 3.5-4.7), fever requiring hospitalisation (HR: 4.4, 95% CI: 3.8-5.0), subsequent neoplasms (HR: 5.7, 95% CI:5.0-6.5), immunological disorders (HR: 6.5, 95% CI:4.5-9.3) and metabolic conditions (HR: 7.1, 95% CI:5.9-8.5).The overall morbidity burden among children was low in general; however, childhood cancer survivors experienced a higher prevalence and subsequent risk of hospitalisation for a range of morbidities. Targeted policies may be required to promote awareness on health vulnerabilities and gender disparity and to improve advocacy for healthcare in deprived communities.Wellcome Trust, National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre and Academy of Medical Sciences. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Impact of public health team engagement in alcohol licensing on health and crime outcomes in England and Scotland: A comparative timeseries study between 2012 and 2019
Authors: Frank de Vocht, Cheryl McQuire, Claire Ferraro, Philippa Williams, Madeleine Henney, Colin Angus, Matt Egan, Andrea Mohan, Richard Purves, Nason Maani, Niamh Shortt, Laura Mahon, Gemma Crompton, Rachel O'Donnell, James Nicholls, Linda Bauld, Niamh Fitzgerald
Journal: The Lancet Regional Health - Europe (2022)

Public health teams (PHTs) in England and Scotland engage to varying degrees in local alcohol licensing systems to try to reduce alcohol-related harms. No previous quantitative evidence is available on the effectiveness of this engagement. We aimed to quantify the effects of PHT engagement in alcohol licensing on selected health and crime outcomes.
Evidence of surface contamination in hospital rooms occupied by patients infected with monkeypox, Germany, June 2022
Authors: Dominik Nörz, Susanne Pfefferle, Thomas T. Brehm, Gefion Franke, Ilka Grewe, Birte Knobling, Martin Aepfelbacher, Samuel Huber, Eva M. Klupp, Sabine Jordan, Marylyn M. Addo, Julian Schulze zur Wiesch, Stefan Schmiedel, Marc Lütgehetmann, Johannes K. Knobloch
Journal: Eurosurveillance (2022)

The extent of monkeypox virus environmental contamination of surfaces is unclear. We examined surfaces in rooms occupied by two monkeypox patients on their fourth hospitalisation day. Contamination with up to 10 5 viral copies/cm 2 on inanimate surfaces was estimated by PCR and the virus was successfully isolated from surfaces with more than 10 6 copies. These data highlight the importance of strict adherence of hospital staff to recommended protective measures. If appropriate, pre-exposure or early post-exposure vaccination should be considered for individuals at risk.
Resolving SARS-CoV-2 CD4+ T cell specificity via reverse epitope discovery
Authors: Mikhail V. Pogorelyy, Elisa Rosati, Anastasia A. Minervina, Robert C. Mettelman, Alexander Scheffold, Andre Franke, Petra Bacher, Paul G. Thomas
Journal: Cell Reports Medicine (2022)

The current strategy to detect immunodominant T cell responses focuses on the antigen, employing large peptide pools to screen for functional cell activation. However, these approaches are labor and sample intensive and scale poorly with increasing size of the pathogen peptidome. T cell receptors (TCRs) recognizing the same epitope frequently have highly similar sequences, and thus, the presence of large sequence similarity clusters in the TCR repertoire likely identify the most public and immunodominant responses. Here, we perform a meta-analysis of large, publicly available single-cell and bulk TCR datasets from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals to identify public CD4
P1232: PRINCIPLES OF PRECISION ONCOLOGY IN PRIMARY REFRACTORY HIGH-GRADE B-CELL LYMPHOMA WITH MYC-, BCL2 AND/OR BCL6 REARRANGEMENTS (HGBL-DH/TH)
Authors: H. Witte, A. Faehnrich, J. Riedl, A. Kuenstner, J. Ketzer, N. von Bubnoff, H. Merz, H. Busch, A. Feller, N. Gebauer
Journal: HemaSphere (2022)

Background: The optimal treatment strategy in primary refractory high-grade B-cell lymphomas with MYC-, BCL2 and/or BCL6rearrangements (prHGBL-DH/TH) remains insufficiently addressed in the light of unfavorable prognosis and recent findings concerning the mutational pathogenesis of this provisional entity. Although there is growing evidence supporting multidisciplinary molecular tumor-boards (MTB) in solid tumors, only a minor subset of MTB recommendations affects hematologic malignancies. Aims: In the present study, we aimed to emphasize the potential of MTB recommendations in HGBL-DH/TH patients (n=19) based on previously published whole exome sequencing (WES) data. Methods: For the annotation of genomic alterations, the institutional MTB pipeline (University Cancer Center Schleswig-Holstein: UCCSH), certified for routine clinical diagnostics, was employed. Consecutive data-base research and annotation according to NCT/DKTK MASTER evidence levels was performed in order to identify molecularly stratified treatment strategies. Results: Median age was 72 (range 35-79) and 68.4% (n=13) were male. Cytogenetically 7/19 cases presented with MYC/BCL2, 5/19 with MYC/BCL6 double-hit-constellation and 7/19 triple-hit lymphomas were included. The standard turn-around time for the MTB pipeline after sampling was 21 days. The applied LymphGen algorithm proposed by Wright et al.revealed the majority of cases (n=13) to correspond to the C3/EZB cluster whereas three cases corresponded to the C1/BN2 cluster and the remaining three cases were not classifiable. Our virtual institutional MTB pipeline identified molecular stratified treatment approaches in 16/19 HGBL-DH/TH cases with NCT/DKTK evidence level of m2A or higher. As proposed by Horak et al., we classified significant mutations in accordance with biomarker/treatment baskets and detected four targetable cell cycle (CC) alterations, two targetable tyrosine kinases (TK) and five others (OTH). Noticeable, 14 mutations affecting chromatin and/or epigenetic modifiers such as EZH2 or IDH1 were annotated as promising therapeutic targets. Moreover, one case presented with relevant BRCAness features suggesting the administration of a PARP-inhibitor such as Olaparib. Each recommended drug was either approved by the FDA and/or EMA or at least designated for FDA/EMA fast track development. Image:Summary/Conclusion: The applied virtual MTB approach revealed molecularly stratified treatment options alongside targetable genomic signatures in the majority of primary refractory HGBL-DH/TH patients. The present results underline the potential relevance of MTB consultations in this difficult-to-treat entity.
PB1966: HEMOPOIETIC NICHE IMPAIRMENT IN TREATED MULTIPLE MYELOMA PATIENTS
Authors: N. Y. Semenova, N. I. Enukashvily, I. I. Kostorma, L. A. Belik, D. V. Baram, V. A. Balashova, S. V. Gritsaev, S. S. Bessmeltsev, D. I. Ostromyshenskii, I. S. Martynkevich
Journal: HemaSphere (2022)

Background: It has been increasingly recognized that cancer progression is not an autonomous process driven and performed exclusively by cancer cells. Hematopoietic cells live in a complex mesenchymal environment ant this environment influences the cancer progression and vice versa is influenced by cancer cells. The tumor-educated microenvironment plays a role in immunosuppression, angiogenesis, and drug resistance. Being in contact with cancer cells, mesenchymal stem/stromal cells acquire cancer-associated phenotype. It is not known whether the hematopoietic niche is restored in multiple myeloma (MM) patients’ bone marrow after treatment. Aims: The aim of the work was to study hematopoietic niche in MM patients with different treatment outcome. Methods: Healthy donors (HD, n=2) and patients (n= 24) with different MRD status after bortesomib based therapy were enrolled in the study. Histological examination was performed on their trephines, bioinformatics analysis of aspirate transcriptomes was performed to analyze non-coding tandemly repeated RNA profile and the level of transcription of genes of WNT family, the results of computational analysis was checked in vitro by qPCR and in situ by DNA-RNA FISH of mesenchymal stem cells (MSC) of patients’ bone marrow. The interaction of of MSC and cancer cells was mimicked in coculture experiment with or without bortezomib. Results: The histology of MM hematopoietic niche of patients with partial response (PoCR) and non-responders (NR) was different from normal - the level of vessels density and a-smooth muscle actin staining (a marker of MSC/fibroblasts with cancer-associated phenotype) were significantly higher than in HD niche. MSC from MM patients were more resistant to bortezomib treatment and more effective in supporting cancer cells viability during incubation with the drug as compare with HD MSC. Moreover, MM MSC have prominent cancer-associated phenotype and increased transcription of some tandemly repeated sequences. We have found that transcription of several WNT family genes was downregulated in NR and PoCR patients. Our results give an evidence that MM hematopoietic niche is not returned to normal after treatment especially in patients non-responding or partially responding to it. Some of the genes of WNT family are involved in ostegenesis and they are downregulated in treated MM patients. Summary/Conclusion: MSC from MM patients have a number of features in morphology, genes and non-coding DNA expression profiles persisted after treatment. The work was supported by by the Ministry of Science and Higher Education of the Russian Federation (project 15.BRC.21.0011, Agreement № 075-15-2021-1063)
COVID-19 Vaccine Provider Availability and Vaccination Coverage Among Children Aged 5–11 Years — United States, November 1, 2021–April 25, 2022
Authors: Jennifer DeCuir, Lu Meng, Yi Pan, Tara Vogt, Kevin Chatham-Stevens, Seth Meador, Lauren Shaw, Carla L. Black, LaTreace Q. Harris
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

COVID-19 can lead to severe outcomes in children, including multisystem inflammatory syndrome, hospitalization, and death (1,2). On November 2, 2021, the Advisory Committee on Immunization Practices issued an interim recommendation for use of the BNT162b2 (Pfizer-BioNTech) vaccine in children aged 5-11 years for the prevention of COVID-19; however, vaccination coverage in this age group remains low (3). As of June 7, 2022, 36.0% of children aged 5-11 years in the United States had received ≥1 of COVID-19 vaccine (3). Among factors that might influence vaccination coverage is the availability of vaccine providers (4). To better understand how provider availability has affected COVID-19 vaccination coverage among children aged 5-11 years, CDC analyzed data on active COVID-19 vaccine providers and county-level vaccine administration data during November 1, 2021-April 25, 2022. Among 2,586 U.S. counties included in the analysis, 87.5% had at least one active COVID-19 vaccine provider serving children aged 5-11 years. Among the five assessed active provider types, most counties had at least one pharmacy (69.1%) or public health clinic (61.3%), whereas fewer counties had at least one pediatric clinic (29.7%), family medicine clinic (29.0%), or federally qualified health center (FQHC)* (22.8%). Median county-level vaccination coverage was 14.5% (IQR = 8.9%-23.6%). After adjusting for social vulnerability index (SVI)† and urbanicity, the analysis found that vaccination coverage among children aged 5-11 years was higher in counties with at least one active COVID-19 vaccine provider than in counties with no active providers (adjusted rate ratio [aRR] = 1.66). For each provider type, presence of at least one provider in the county was associated with higher coverage; the largest difference in vaccination coverage was observed between counties with and without pediatric clinics (aRR = 1.37). Ensuring broad access to COVID-19 vaccines, in addition to other strategies to address vaccination barriers, could help increase vaccination coverage among children aged 5-11 years.
Migrants’ primary care utilisation before and during the COVID-19 pandemic in England: An interrupted time series analysis
Authors: Claire X. Zhang, Yamina Boukari, Neha Pathak, Rohini Mathur, Srinivasa Vittal Katikireddi, Parth Patel, Ines Campos-Matos, Dan Lewer, Vincent Nguyen, Greg C.G. Hugenholtz, Rachel Burns, Amy Mulick, Alasdair Henderson, Robert W. Aldridge
Journal: The Lancet Regional Health - Europe (2022)

How international migrants access and use primary care in England is poorly understood. We aimed to compare primary care consultation rates between international migrants and non-migrants in England before and during the COVID-19 pandemic (2015-2020).